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First- v. second-generation antipsychotics and risk for diabetes in schizophrenia: systematic review and meta-analysis

Department of Psychological Medicine, Institute of Psychiatry, London, UK

D. Hopkins, FRCP

Department of Diabetic Medicine, King's College Hospital, London, UK

R. C. Peveler, MA, DPhil, FRCPsych

Clinical Neurosciences Division, University of Southampton, Southampton, UK

R. I. G. Holt, FRCP, FHEA, PhD

Endocrinology and Metabolism Sub-division, University of Southampton, Southampton, UK

M. Woodward, PhD

Department of Medicine, Mount Sinai Medical Center, New York, USA

K. Ismail, PhD, MRCPsych

Department of Psychological Medicine, Institute of Psychiatry, King's College London, UK

Correspondence: M. Smith, Department of Psychological Medicine, Institute of Psychiatry, King's College London, London SE5 9RJ, UK. Email: m.smith{at}iop.kcl.ac.uk

Declaration of interest

R.P. has received fees for speaking and consulting from makers of antipsychotics, including Eli Lilly and Company, Bristol Myers Squibb, Sanofi, Pfizer, Janssen and Astra Zeneca. R.H. has received educational grants and fees for lecturing and consultancy work from Eli Lilly and Company, Bristol Myers Squibb and GlaxoSmithKline.

Background

The increased prevalence of diabetes in schizophrenia is partly attributed to antipsychotic treatment, in particular second-generation antipsychotics, but the evidence has not been systematically reviewed.

Aims

Systematic review and meta-analysis comparing diabetes risk for different antipsychotics in people with schizophrenia.

Method

We searched MEDLINE, PsycINFO, EMBASE, International Pharmaceutical Abstracts, CINAHL and Web of Knowledge until September 2006. Studies were eligible for inclusion if the design was cross-sectional, case–control, cohort or a controlled trial in individuals with schizophrenia or related psychotic disorders, where second-generation antipsychotics (defined as clozapine, olanzapine, risperidone and quetiapine) were compared with first-generation antipsychotics and diabetes was an outcome. Data were pooled using random effects inverse variance weighted meta-analysis.

Results

Of the studies that met the inclusion criteria (n=14), 11 had sufficient data to include in the meta-analysis. Four of these were retrospective cohort studies. The relative risk of diabetes in patients with schizophrenia prescribed one of the second-generation v. first-generation antipsychotics was 1.32 (95% CI 1.15–1.51). There were insufficient data to include aripiprazole, ziprasidone and amisulpride in this analysis.

Conclusions

There is tentative evidence that the second-generation antipsychotics included in this study are associated with a small increased risk for diabetes compared with first-generation antipsychotics in people with schizophrenia. Methodological limitations were found in most studies, leading to heterogeneity and difficulty interpreting data. Regardless of type of antipsychotic, screening for diabetes in all people with schizophrenia should be routine.

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